New Instrument Captures the Secret Lives of Cells

A new microscopy technique could change the way scientists understand dozens of vital processes.

This video shows the coordinated activity of the protein actin (magenta), and myosin (green), which is involved in muscle contractions. Working together, the proteins form a network of filaments that create forces needed for cells to move.

On the surface of a living cell at any given time, hundreds of tiny bubbles are popping into existence, surrounding and incorporating proteins, hormones, fats, and the occasional bacteria or virus. But until now the details of this activity were inferred – you couldn’t actually see it. The problem wasn’t just that the structures taking part in this bustling activity are too small, but that our bodies work on an invisibly fast time scale—important changes are taking place over fractions of a second.

Two years ago, Harvard cell biologist Thomas Kirchhausen attended a talk that convinced him that capturing all this molecular-level action was possible. The speaker was Eric Betzig of the Howard Hughes Medical Institute’s Janelia Research Campus in Virginia. A few months later, Betzig shared the 2014 Nobel Prize in chemistry for advances in high resolution microscopy, but the talk that Kirchhausen attended was about something different—another technique called SIM (structured illumination microscopy), which is used to make movies.

The Nobel work involved the use of fluorescent molecules that tag different parts of the cells. But doing so exposes cells to much more intense light than they evolved to function under. “That harms cells, kills cells, and in the worst cases, actually vaporizes the cells,” Betzig said. The new technique, SIM, pushes the limits of time resolution while going easy on the cells.

Today in the journal Science, Betzig and Kirchhausen, along with collaborators in the U.S. and China, published a series of images of the bustling inner workings of cells using some new twists on SIM.

“The hallmark of life is that it’s animated,” says Betzig. “There’s only so much you can learn from something that’s fixed and dead, no matter how good your resolution is.”

This video shows the process by which cells take in different kinds of molecules. A protein called clathrin controls the formation of little bubbles that engulf various substances the cell needs to import. In the second part of the movie, different colors correspond to the ages of the bubbles, which are called clathrin pits.

Here, the video shows a monkey kidney cell and highlights two types of proteins – clathrin, in green, and a protein called actin, in red. Cell biologists don’t agree on what, exactly, actin does when cells take in proteins and other molecular cargo, so movies like this can help clarify its role.